Coronary heart disease (CHD) is the major cause of death in American women, and every year a similar number of women and men die due to CHD. Growing evidence supports important differences in the pathophysiology, clinical presentation and prognosis of CHD between women and men;yet much remains to be learned about the unique characteristics of CHD in women. Young and middle-aged women have higher mortality and complication rates after an acute myocardial infarction (MI) compared with men of similar age. Reasons for these differences are unknown;they are not explained by traditional CHD risk factors, other comorbidity or treatments, and occur despite the fact that women have less coronary atherosclerosis and more preserved ventricular function than men. One third to two thirds of patients with CHD have myocardial ischemia that is induced by psychological stressors. Such ischemia is often painless and unrelated to severity of coronary artery disease;nonetheless it is associated with adverse outcomes. Emotional factors such as depression and psychological trauma are more common in women with CHD than in men and may predispose women to stress-induced ischemia. Depression, for example, is present in up to 40% of women with MI younger than 60 years. However, emotionally-triggered ischemia has hardly been studied in women before. The overall objective of this proposal is to evaluate differences in stress-induced ischemia between 50 women and 50 men younger than 60 years who were hospitalized for acute MI in the previous 6 months in Emory- affiliated hospitals. We hypothesize that myocardial ischemia due to emotional factors is more common in women than in men, while exercise-induced ischemia is as common, or even less common, in women. The aims of this study are: (1) Using single photon emission tomography (SPECT) [Tc-99m] sestamibi myocardial perfusion imaging, to compare myocardial perfusion during rest, during exercise, and during an emotionally stressful challenge in women and men. (2) To investigate biological mechanisms for the sex differences in ischemia induced by emotional stress, including differences in hemodynamic (blood pressure, heart rate), neurobiological (cortisol and autonomic nervous system) and inflammatory responses to the stressful challenge. (3) To investigate behavioral/psychosocial explanatory factors for the sex differences in ischemia induced by emotional stress (depression, history of trauma, and socio-economic environment). Younger women with MI represent an understudied patient group despite their higher rate of adverse events compared with men. Investigation of this group will provide critical information for the prevention of CHD in women. Our study may uncover a unique pathway which may explain sex differences in the outcome of MI. PUBLIC HEALTH RELEVANCE: Coronary heart disease is the major cause of death in American women and yet, much remains to be learned about the unique characteristics of this disease in women. Young and middle-aged women have higher mortality and complication rates after an acute myocardial infarction (MI) and higher burden of psychosocial risk factors. This study will evaluate whether emotionally triggered ischemia is more common in women than in men after MI, whether it is correlated with psychosocial risk factors that are common in women, such as depression and history of trauma, and whether it is associated with biological changes that may have prognostic significance, such as hemodynamic, neurobiological and inflammatory responses to stress.